P563: A RANDOMIZED, DOUBLE-BLIND, 2-ARM, MULTICENTER, PH3 STUDY OF VENETOCLAX &amp; ORAL AZACITIDINE VS. ORAL AZACITIDINE AS MAINTENANCE THERAPY FOR PTS WITH AML IN FIRST REMISSION AFTER INTENSIVE CHEMOTHERAPHY
Authors: V. Ivanov, S.-P. Yeh, J. Mayer, L. Saini, A. Unal, M. Boyiadzis, D. M. Hoffman, K. Kang, S. N. Addo, W. L. Mendes, A. T. Fathi
Journal: HemaSphere (2022)

Background: Acute myeloid leukemia (AML) is an aggressive, heterogenous hematologic malignancy with poor prognosis. For eligible patients, standard treatment includes intensive chemotherapy during induction, followed by consolidative chemotherapy or stem cell transplantation. Despite current therapies, the prevention of relapse is still a major therapeutic challenge and an unmet need for patients in remission. Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor that induces apoptosis in AML cells. Ven in combination with Azacitidine (Aza) leads to prolonged overall survival (OS) and rapid, durable remissions in treatment-naïve AML patients ineligible for intensive chemotherapy. The QUAZAR AML-001 (NCT01757535) trial showed that the median OS in patients receiving maintenance oral Aza was superior to patients receiving placebo following upfront induction and consolidation; this benefit was also observed for patients who achieved either complete remission (CR) or CR with incomplete blood count recovery (CRi). VIALE-M is a randomized, double-blind, two-part study (NCT04102020) to determine the recommended Phase 3 dose (RPTD) of Ven in combination with oral Aza (CC-486) that can be safely administered as maintenance therapy, and to evaluate the safety and efficacy of Ven in combination with oral Aza + BSC compared to placebo and oral Aza + BSC in patients with AML who have achieved CR or CRi after intensive induction and consolidation. Aims: N/A Methods: The study is enrolling patients aged ≥18 years with newly diagnosed AML per WHO 2016 classification, with confirmed CR or CRi following intensive induction and consolidation therapies, from > 200 sites worldwide. Patients must have achieved first CR or CRi (after induction) ≤120 days of first dose of study drug or ≤75 days past last dose of last consolidation cycle, have intermediate or poor risk cytogenetics per NCCN 2016 categorization, ECOG ≤2, and no history of acute promyelocytic leukemia or active central nervous system involvement with AML. For the dose finding part of the study, patients will receive Ven QD for up to 24 cycles and oral Aza QD on D1-14 of each 28-day cycle for up to 24 cycles to determine the RPTD. For safety expansion, patients will receive Ven QD for up to 24 cycles and oral Aza QD on D1-14 of each cycle for up to 24 cycles at the RPTD. For the randomization part, patients will be randomized 1:1 to receive placebo or Ven QD at the RTPD and oral Aza QD on D1-14 of each cycle for 24 cycles. In all parts, treatment may discontinue due to relapse/unacceptable toxicity, or continue beyond 24 cycles under investigator’s discretion. For the randomization portion, the primary endpoint is relapse-free survival; secondary outcomes include OS, minimal residual disease conversion, and improvement in quality of life. Results: N/A Summary/Conclusion: N/A